PXD024438

PXD024438 is an original dataset announced via ProteomeXchange.

Title	Switch in Cytochrome C Oxidase Composition Provides Host Protection during Acute Infection
Description	Mitochondria play integral roles in the control of inflammation. Mito-SEPs are small open reading frame-encoded peptides that localize to the mitochondria to regulate oxidative metabolism. Motivated by our observation that mito-SEPs are negatively associated with inflammation, we performed a proteo-genomic mito-SEP screen in human aortic endothelial cells to find mito-SEPs that promote resolution of inflammation. Here, we report the discovery of MOCCI (Modulator of Cytochrome C oxidase during Inflammation), an Interleukin-1β-induced mito-SEP encoded by the C15ORF48 gene. MOCCI is a paralog of NADH:Ubiquinone Oxidoreductase Complex Assembly Factor 4 (NDUFA4), the 14th subunit of the mitochondrial respiratory chain Complex IV (CIV). During inflammation, MOCCI displaces NDUFA4 in CIV, aided by repression of NDUFA4 mRNA by a microRNA miR-147b encoded within the 3’ untranslated region of C15ORF48. MOCCI lowers membrane potential and ROS production with overall cyto-protective and anti-inflammatory effects. In parallel, miR-147b exerts a strong anti-viral effect by enhancing RIG-I/MDA-5 pathway of viral recognition and induction of the interferon response. Our findings demonstrate how the coding and non-coding functions of C15ORF48 coordinate to regulate the composition and activity of Complex IV to limit pathogen replication and host inflammation during acute infection. We propose that Complex IV modulation via MOCCI-miR147b is a potential strategy for ameliorating viral-induced hyper-cytokinemia and host immunopathology.
HostingRepository	PRIDE
AnnounceDate	2021-03-08
AnnouncementXML	Submission_2021-03-08_15:34:17.216.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Stroud
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-01 06:13:36	ID requested
⏵ 1	2021-03-08 15:34:17	announced

Dataset with its publication pending

submitter keyword: Mouse, Mitochondria, TMT, LC-MS/MS

David Stroud
contact affiliation	Department of Biochemistry and Pharmacology, The Bio21 Molecular Science & Biotechnology Institute, University of Melbourne, Melbourne, Australia
contact email	david.stroud@unimelb.edu.au
lab head
David Stroud
contact affiliation	The University of Melbourne
contact email	david.stroud@unimelb.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024438
     1. Label: PRIDE project
     2. Name: Switch in Cytochrome C Oxidase Composition Provides Host Protection during Acute Infection